1. Field of the Invention
This invention relates to 1-(benzothiazol-2-yl)-4-(1-phenylmethyl)piperazines and pharmaceutical compositions containing such compounds. It also relates to the use of such compounds in the treatment or prevention of psychotic disorders such as schizophrenia and other central nervous system diseases.
2. Description of the Related Art
The therapeutic effect of conventional antipsychotics, known as neuroleptics, is generally believed to be exerted through blockade of dopamine receptors. However, neuroleptics are frequently responsible for undesirable extrapyramidal side effects (EPS) and tardive dyskinesias, which are attributed to blockade of D.sub.2 receptors in the striatal region of the brain. The dopamine D.sub.4 receptor subtype has recently been identified (Nature, 350: 610 (Van Tol et al., 1991); Nature, 347: 146 (Sokoloff et al., 1990)). Its unique localization in limbic brain areas and its differential recognition of various antipsychotics indicates that the D.sub.4 receptor plays a major role in the etiology of schizophrenia. Selective D.sub.4 antagonists are considered effective antipsychotics free from the neurological side effects displayed by conventional neuroleptics.
J. Heterocycl. Chem., 32: 707-718 (Orjales et al., 1995) discloses piperazinebenzothiazole derivatives said to be useful as antihistaminics.
J. Med. Chem., 37: 1320-1325 (Monge et al., 1994) discloses piperazinebenzothiazole derivatives as 5-HT.sub.3 antagonists and 5-HT.sub.4 agonists.
Published International Application WO 9420494 discloses piperazinebenzothiazole derivatives said to be capable of stimulating gastrointestinal motility.